The major investigative goal of the Department of Cardiology at Cedars-Sinai Medical Center relates to studies of patients with coronary artery disease, with particular reference to appropriate therapeutic interventions. The goals of this program project grant form an important element of the overall departmental goals, and are intended to study the physiologic consequences of cardiac ischemia, with particular reference to therapeutic implications. The animal and patient studies focus on studies of regional ischemia, reversibility of ischemia, effects of antiarrhythmic agents, alterations in coronary blood flow, changes in cardiac compliance and indices of mechanical performance, alterations in patterns of AV conduction, effects of counterpulsation and alterations in ventricular performance following coronary revascularization. Most projects in the program include a multidisciplinary approach involving mechanics, hemodynamic and flow measurements, metabolism, electrophysiology, pharmacology and biochemistry. Dog studies of regional ischemia employ epicardial strain gauges and length gauges and include measurements of coronary sinus blood flow by the continuous thermodilution techniques. In vitro studies of pharmacology and electrophysiology will utilize isolated cat and canine heart muscle. Studies of AV conduction patterns and hemodynamic evaluations before and after coronary revascularization are conducted in the cardiac catheterization laboratory. In summary, it is anticipated that our continued efforts will provide a more detailed description of the physiologic consequences of cardiac ischemia, and will thus provide more rational guidelines for the therapy of patients with acute and chronic coronary artery disease. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application. BIBLIOGRAPHIC REFERENCES: Bassan M, Ganz W, Marcus HS and Swan HJC: The effect of intracoronary injection of contrast medium upon coronary blood flow. Circulation 51:442-445, 1975. Nagasawa K, Vyden JK, Forrester JS, Groseth-Dittrich MF, Corday E and Swan HJC: Effect of phentolamine on cardiac performance and energetics in acute myocardial infarction. Circ Shock 2:5-11, 1975.